AB0873 WHOLE BODY INSULIN SENSITIVITY IS INCREASED IN SYSTEMIC SCLEROSIS
Authors: J. Ciaffi, P. Ruscitti, I. Di Cola, V. Pavlych, N. Italiano, M. Gentile, M. Tomassetti, T. Huizinga, J. De Vries-Bouwstra, F. Ursini, P. Cipriani
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The prevalence of type 2 diabetes (T2D) is increased in rheumatoid arthritis (RA) and other inflammatory diseases, while the available evidence suggests that in systemic sclerosis (SSc) it is lower than in the general population [1]. Insulin resistance and ß-cell dysfunction are the main mechanisms in the pathophysiology of T2D. However, mechanisms underlying the negative association between SSc and T2D have not been elucidated. <h3>Objectives</h3> We aimed to evaluate whole-body insulin sensitivity in SSc patients and to compare the results with controls with no autoimmune rheumatic disease (non-ARD) and with patients affected by RA. Additionally, we investigated whether insulin sensitivity was associated with SSc characteristics. <h3>Methods</h3> The study population was composed of consecutive adult SSc patients. For comparison, non-ARD and RA patients were included. All were screened for T2D before inclusion. Individuals with a diagnosis of diabetes and those using corticosteroids or insulin-sensitizing agents were excluded. The whole-body insulin sensitivity index (ISI) was estimated from glucose and insulin concentrations obtained during the oral glucose tolerance test (OGTT) using the equation proposed by Matsuda [2], which is validated against euglycemic insulin clamp and provides reliable estimates of glucose homeostasis. Insulin resistance (HOMA-IR) was calculated. <h3>Results</h3> A total of 41 SSc patients, 41 individuals with RA and 82 non-ARD control patients were recruited. SSc patients were significantly older and had lower BMI than controls with RA, but had comparable characteristics with non-ARD patients (Table 1). The ISI was significantly higher in SSc patients compared with RA controls [8.01 (4.85 – 12.62) vs 3.39 (1.93 – 6.14), p &lt;0.001] and with non-ARD patients [8.01 (4.85 – 12.62) vs 4.38 (3.39 – 6.37), p &lt;0.001]. Significant differences emerged also when analysing the HOMA-IR, which was lower in SSc patients than in RA [0.98 (0.66 – 1.52) vs 2.02 (1.36 – 3.63), p &lt;0.001] and non-ARD [0.98 (0.66 – 1.52) vs 1.74 (1.28 – 2.28), p &lt;0.001]. In normal weight individuals (BMI from 18.5 to 24.9), median ISI was higher in the SSc group than in RA (p =0.007) and non-ARD controls (p &lt;0.001). In overweight and obese cases (BMI ≥25) ISI was also higher in the SSc group than in RA (p =0.003) and non-ARD controls (p =0.017) (Figure 1). In the SSc group, patients with diffuse cutaneous disease had significantly higher ISI than individuals with limited cutaneous SSc [11.60 (8.59 – 20.13) vs 6.58 (4.91 – 11.63), p = 0.027]. In univariate analysis, ISI was significantly correlated with BMI (rho= -0.468, p= 0.002), fasting insulin (rho= -0.715, p &lt;0.001), and modified Rodnan skin score (rho= 0.422, p= 0.006. In multiple linear regression model adjusted for BMI and fasting plasma insulin, the association between ISI and modified Rodnan skin score was lost (r<sup>2</sup> = 0.27, p= 0.095). <h3>Conclusion</h3> The findings of our study suggest that patients with SSc are more insulin sensitive than those with RA and even than individuals without inflammatory diseases. This is the first time that whole-body insulin sensitivity is assessed in SSc using a validated and reliable method, contributing unique data to the knowledge about glucose homeostasis in SSc. <h3>References</h3> [1]Ngian G-S et al. Prevalence of coronary heart disease and cardiovascular risk factors in a national cross-sectional cohort study of systemic sclerosis. Annals of the Rheumatic Diseases 2012. [2]Matsuda M et DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.